Gemcitabine is a nuceloside analogue that has been effectively used for the treatment of cancers including non-small cell lung cancer, pancreatic cancer, bladder cancer, ovarian cancer and breast cancer. Despite gemcitabine's demonstrated efficacy in a number of clinical situations, the drug is also associated with side effects such as flu-like symptoms, diarrhea, weakness, mouth sores, and shortness of breath. In order to maximize the benefits of gemcitabine-based chemotherapy regimens and improve safety and tolerability, new forms of gemcitabine are needed. The present invention, providing surprisingly effective gemcitabine derivatives, meets this and other needs.